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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Reproductive Biology and Endocrinology 1/2012

Down-regulation of the transcription factor snail in the placentas of patients with preeclampsia and in a rat model of preeclampsia

Zeitschrift:
Reproductive Biology and Endocrinology > Ausgabe 1/2012
Autoren:
Larisa Fedorova, Cara Gatto-Weis, Sleiman Smaili, Nauman Khurshid, Joseph I Shapiro, Deepak Malhotra, Terrence Horrigan
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1477-7827-10-15) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

LF participated in the study design, carried out experiments and prepared the manuscript. CGW performed histopathological and immunohistochemical analysis and contributed to the manuscript preparation. SS and NK collected the human placenta samples, extracted placental proteins and participated in Western blotting analysis. JIS and TH formulated the research questions, conceived the study and participated in drafting of the manuscript. DM participated in the development of critical methodology and the manuscript preparation. All authors read and approved the final manuscript.

Abstract

Background

Placental malfunction in preeclampsia is believed to be a consequence of aberrant differentiation of trophoblast lineages and changes in utero-placental oxygenation. The transcription factor Snail, a master regulator molecule of epithelial-mesenchymal transition in embryonic development and in cancer, is shown to be involved in trophoblast differentiation as well. Moreover, Snail can be controlled by oxidative stress and hypoxia. Therefore, we examined the expression of Snail and its downstream target, e-cadherin, in human normal term, preterm and preeclamptic placentas, and in pregnant rats that developed preeclampsia-like symptoms in the response to a 20-fold increase in sodium intake.

Methods

Western blotting analysis was used for comparative expression of Snail and e- cadherin in total protein extracts. Placental cells expressing Snail and e-cadherin were identified by immunohistochemical double-labeling technique.

Results

The levels of Snail protein were decreased in human preeclamptic placentas by 30% (p < 0.01) compared to normal term, and in the rat model by 40% (p < 0.001) compared to control placentas. In preterm placentas, the levels of Snail expression varied, yet there was a strong trend toward statistical significance between preterm and preeclamptic placentas. In humans, e-cadherin protein level was 30% higher in preeclamptic (p < 0.05) placentas and similarly, but not significantly (p = 0.1), high in the preterm placentas compared to normal term. In the rat model of preeclampsia, e-cadherin was increased by 60% (p < 0.01). Immunohistochemical examination of human placentas demonstrated Snail-positive staining in the nuclei of the villous trophoblasts and mesenchymal cells and in the invasive trophoblasts of the decidua. In the rat placenta, the majority of Snail positive cells were spongiotrophoblasts of the junctional zone, while in the labyrinth, Snail-positive sinusoidal giant trophoblasts cells were found in some focal areas located close to the junctional zone.

Conclusion

We demonstrated that human preeclampsia and the salt-induced rat model of preeclampsia are associated with the reduced levels of Snail protein in placenta. Down-regulation of the transcription factor Snail in placental progenitor cell lineages, either by intrinsic defects and/or by extrinsic and maternal factors, may affect normal placenta development and function and thus contribute to the pathology of preeclampsia.
Zusatzmaterial
Authors’ original file for figure 1
12958_2011_950_MOESM1_ESM.pdf
Authors’ original file for figure 2
12958_2011_950_MOESM2_ESM.pdf
Authors’ original file for figure 3
12958_2011_950_MOESM3_ESM.pdf
Authors’ original file for figure 4
12958_2011_950_MOESM4_ESM.pdf
Literatur
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